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At least 19 recordsLinked to original sources
PubMed2003

From thiourea to bicyclic structures: an original route to imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines.

We report an example of an efficient regioselective synthesis of biheterocyclic compounds using thiourea as starting material. In fact, N,N'-bis(dimethylaminomethylene)thiourea (1), easily prepared by double condensation of N,N-dimethylformamide dimethyl acetal with thiourea, can be reacted with haloketones or acrylic dienophiles to give thiazolic (2) and thiazinic (3) diazadienes, respectively, themselves undergoing cyclization reactions to yield imidazo[2,1-b]thiazoles, 5H-thiazolo[3,2-a]pyrimidines, 7H-imidazo[2,1-b][1,3]thiazines, and 2H,6H-pyrimido[2,1-b][1,3]thiazines without any regioisomeric ambiguity. This straightforward route represents an original and unambiguously regioselective pathway to these valuable heterocycles.

Journal Article↗
PubMed2000

Novel methods for the facile construction of 3,3-disubstituted and 3, 3-spiro-2H,4H-benzo[e]1,2-thiazine-1,1-diones: synthesis of (11S,12R, 14R)-2-fluoro-14-methyl-11-(methylethyl)spiro[4H-benzo[e]- 1, 2-thiazine-3,2'-cyclohexane]-1,1-dione, an agent for the electrophilic asymmetric fluorination of aryl ketone enolates.

Novel methods for the facile construction of 3,3-disubstituted and 3, 3-spiro 2H,4H-benzo[e][1,2]thiazine-1,1-diones 8a-h are described. o-Methyl lithiation of N-Boc-o-toluenesulfonamide 6 followed by reaction with a variety of ketones gave the corresponding carbinol sulfonamides 7a-g, which underwent cyclization under acidic (methanesulfonic acid) or neutral (NaI/TMSCl/MeCN) conditions to afford the sultams 8a-h in high yields. The chiral spiro sultams 8g, h were subjected to FClO(3) fluorination to give the N-fluorosultams 11a,b, respectively, which were tested for electrophilic asymmetric fluorination of aryl ketone enolates. As a result, the N-fluorosultam 11a exhibited modest asymmetric inducing abilities with the highest ee, reaching 70% for enantioselective fluorination of the lithium enolate of 2-methyl-1-tetralone.

Anti-Infective Agents↗
PubMed1988

Nucleosides of 1,4-thiazin-3-one and derivatives as tetrahedral intermediate analogues of enzymes in pyrimidine nucleoside metabolism.

Reaction of the trimethylsilylated derivative of 1,4-thiazin-3-one with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of SnCl4 gave, after deblocking, 4-beta-ribofuranosyl-1,4-thiazin-3-one (8). Treatment of 1,4-thiazin-3-one with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose in the presence of sodium hydride provided, after deblocking, the corresponding 2-deoxy-beta-D-ribofuranosyl derivatives (19). Oxidation of 4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-thiazin-3-one (7) with 1 equiv of m-chloroperbenzoic acid resulted in 4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-thiazine-2,3-dione (9) and 4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,4-thiazin-3-one 1-oxide (10). Evidence is presented that indicates that the oxidation of the thiazine at the 2-position is due to a Pummerere rearrangement. The new compounds failed to show significant activity against tumor cell lines in culture, L1210 cells in vivo, virus cytotoxicity in cell culture, or cytidine deaminase.

Animals↗
PubMedDate not supplied

Interaction of protonated anticancer thiazines with water-insoluble phospholipids and antineoplastic agents.

A series of neuroleptic protonated phenothiazine derivatives (promethazine, promazine, triflupromazine, methotrimeprazine, propiomazine, trifluoperazine and fluphenazine), some with known anticancer properties, were complexed with water-insoluble antineoplastice agents such as 5-fluorouracil (5FU), methotrexate (MTX) and sulindac, as well as with components of biomembrane and synthetic phospholipids as possible models of cancer and microbial cells. In all cases water-soluble micellar inclusion adducts were formed exhibiting electron charge transfer complex behaviour, with the appearance of thazine free radicals. The thiazines sequestered the drugs and phospholipids in well-defined molar ratios (MR) parabolically-dependent on the dipole moments (mu) of the protonated phenothiazine derivatives. pH comparisons showed that the inclusion adducts followed a model in which the compounds were enveloped in the lipophilic interior of the thiazine aggregates, while the side-chains of the latter faced the aqueous environment. In the model experiment, interaction of the thiazines and the 5FU adducts with E. coli F' lac was additive to marginally synergistic, confirmed by the checkerboard technique. The parabolic dependence of the molar minimum inhibitory concentration of the thiazines and thiazine/5FU adducts on the thiazine dipole moments suggests that their primary loci of interaction are the cell wall or membrane phospholipid components. Thiazines, especially those with dipole moments centered on about 6 D, near which the lowest MR occurs, can act as effective carriers for insoluble or sparsely soluble drugs. Any new thiazine drug for use alone or as a carrier in anticancer therapy should be designed with this criterion in mind.

Antineoplastic Agents↗
PubMed2002

Is immunostaining for Helicobacter pylori superior to the special stain thiazine in detecting small numbers of H. pylori in gastric biopsies?

Helicobacter pylori is implicated in the pathogenesis of gastritis and duodenal ulcers, gastric lymphoma of the mucosa-associated lymphoid tissue (MALT) type, and gastric adenocarcinoma. Eradication of H. pylori with antibiotic therapy therefore is essential, not only for the successful treatment of active gastritis, but also for the treatment and prevention of the MALT lymphoma. It has been suggested recently that immunostaining for H. pylori is more sensitive than special stains for the detection of the organism in the gastric biopsies after triple therapy. Fifty-five endoscopic mucosal biopsies from 38 patients, including 18 treated with H. pylori eradication therapy, were selected for immunostaining because they were either negative or contained rare H. pylori organisms by thiazine stain. Formalin-fixed, paraffin-embedded tissue sections were immunostained for H. pylori using a polyclonal antibody using standard immunoperoxidase technique. The results were compared with those obtained with the thiazine stain. Detection of H. pylori by immunostaining was easier and less time-consuming than by thiazine stain. There was complete agreement between immunostaining and thiazine stain in 48 (87%) cases. Of the 7 discordant cases, 3 (42%) were positive for H. pylori with thiazine only and 4 (48%) with immunostaining only. Given the nature of the selection of the study sample (absent to rare by thiazine stain), the discordance most likely represents a sampling error. The authors concluded that immunostaining for H. pylori did not appear to be more sensitive than special stains. Three cases with bacterial clumps were diagnosed previously as positive for H. pylori, but identified correctly as negative using both staining methods. Pathologists, however, should balance the added cost to patients of immunostaining against the time saved by the easier screening of the immunostained slides and the possibility of false positive results when special stains are interpreted by inexperienced pathologists.

Biopsy↗
PubMed1992

Synthesis of 3-substituted 2-oxo-1,4-thiazines and evaluation of their protective effect against endotoxin shock in mouse.

5-Methyl-2,3-dioxo-2H,4H-1,4-thiazine (7) was obtained by the oxidation of 5-methyl-2H-1,4-thiazin-3(4H)-one (5) with m-chloroperbenzoic acid in MeOH, followed by acid hydrolysis of the resulting 2,2-dimethoxy-1,4-thiazine (6). 3-Chloro-2-oxo-1,4-thiazine (10), which was obtained from 7 by heating with phosphorous oxychloride, reacted with various nucleophiles to give 3-substituted 2-oxo-1,4-thiazines (11a--y). Some of these 2-oxo-1,4-thiazines, 11a--b, e, o and r--s, showed a protective effect against endotoxin shock in D-galactosamine-sensitized mice.

Animals↗
PubMed1998

Mechanistic Studies on the Formation of Thiazolidine and Structurally Related Thiazines in a Cysteamine/2,3-Butanedione Model System.

Phosphate was found to dramatically enhance the formation of 2-methyl-2-acetylthiazolidine from a cysteamine/2,3-butanedione model system. In addition to the major component, 2-methyl-2-acetylthiazolidine, significant amounts of two structurally closely related compounds, 2-acetyl-2,3,5,6-tetrahydro-1,4-thiazine and 5-acetyl-2,3-dihydro-1,4-thiazine, were characterized by using GC/MS (CI and EI). There was an oxidative transformation of 2-acetyl-2,3,5,6-tetrahydro-1,4-thiazine to 5-acetyl-2,3-dihydro-1,4-thiazine in the presence of azodicarbonamide. A formation mechanism for 2-methyl-2-acetylthiazolidine and structurally related 2-acetyl-2,3,5,6-tetrahydro-1,4-thiazine and 5-acetyl-2,3-dihydro-1,4-thiazine is proposed.

Journal Article↗
PubMed1981

Syntheses and pharmacological analysis of new derivatives of tetrahydro-[1,3]-thiazine and 2-thiobarbituric acid.

Three groups of compounds:1,3-thiazine derivatives, 2-thiobarbituric acid derivatives and noncyclic thioureide were obtained as a result of condensation of some N, N1-derivatives of thiocarbamide and malonyl dichlorides, depending on the reaction conditions and chemical character of reagents. It was observed that the substituents beside nitrogen atoms of thiocarbamides, the kind of acid chloride and reaction conditions influenced the course of reaction. The structure of the newly synthesized compounds was proved by the analysis of PMR spectrum and the interpretation of IR spectrum. In the performed pharmacological examination immunotropic and anti-inflammatory activity of these compounds was determined. Among 1,3-thiazine derivatives, 5,5-diallyl-2-phenylimino-3-phenyl-2,3,4,5-tetrahydro-[1,3]-thiazine-4,6-dione and 5,5-diethyl-2-phenylimino-3-naphtyl-2,3,4,5-tetrahydro-[1,3]-thiazine-4,6-dione exhibited anti-inflammatory activity. The compounds also contained the immunotropic component, either stimulatory or suppressive, 2-thiobarbituric acid derivatives displayed stronger anti-inflammatory activity correlated mostly with the immunosuppressive activity. Some interdependence between chemical structure and biological activity in the group of the investigated 1,3-thiazines and 2-thiobarbituric acid derivatives was observed.

Animals↗
PubMed2002

Synthesis of 1,3-thiazine derivatives and their evaluation as potential antimycobacterial agents.

A series of eight 5,6-dihydro-4H-1,3-thiazine derivatives was synthesized by the BF3 x Et2O-catalyzed reaction of selected alpha,beta-unsaturated ketones with thiobenzamide at room temperature. The antimycobacterial activities of these compounds were determined against Mycobacterium tuberculosis H37Rv (ATCC 27294) using the Alamar blue susceptibility assay. Three compounds, 5-hydroxy-3-phenyl-4-aza-2-thiabicyclo[3.3.1]none-3-ene 3a, 4-hydroxy-4-methyl-6-pentyl-2-phenyl-5,6-dihydro-4H-1,3-thiazine 3b, and 4-ethyl-4-hydroxy-2-phenyl-5,6-dihydro-4H-1,3-thiazine 3c exhibited inhibitory activities of 97, 77 and 76%, respectively, at a concentration of 6.25 microg/ml. The actual MIC99 for the most active of these compounds, 3a, was also determined to be >6.25 microg/ml. These results, and especially those for 3a, suggest that 1,3-thiazines are potential lead compounds in the search for new antitubercular agents.

Antitubercular Agents↗
PubMed1980

Pharmacological activity in the group of new pyrido-[2,3-c]-1,2 thiazine 1,1-dioxide derivatives.

Influence of 25 newly synthesized pyrido-1,2 thiazine 1,1-dioxide derivatives on immunological response and on induced inflammatory processes was studied. Marked immunostimulative activity (PFC) of 4,6-dimethyl-8-phenyl-2H-pyrido-[2,3-c]-thiazine dioxide (preparation X) was noted. Strong immunosuppressive activity connected with antiinflammatory activity (xylene, carrageenin and granulation test) was observed after the animals had been treated with 2-2'-(dimethyl-aminoethyl)-4,6-dimethyl-7-methoxy-8-phenyl-2H-pyrido-[2,3-c]-1, 2 thiazine 1,1-dioxide (preparation VIII) as well as 2,4,6-trimethyl-8-3H-thiazine dioxide (preparation XX). Mechanism of the activity of these compounds is discussed. In the group of the tested derivatives, relatively limited dependence between biological effects and chemical structure of the compounds was demonstrated.

Adjuvants, Immunologic↗
PubMed1997

In situ hybridization for Helicobacter pylori in gastric mucosal biopsy specimens: quantitative evaluation of test performance in comparison with the CLOtest and thiazine stain.

Numerous detection methods for Helicobacter Pylori (H. pylori) have been developed with varying degrees of purported diagnostic utility. We have developed a rapid nonradioactive in situ hybridization (ISH) method for H. pylori detection in paraffin-embedded tissue and assessed its relative diagnostic performance by receiver operator characteristics (ROC) in comparison to the thiazine stain and CLOtest. Forty-five patients undergoing endoscopy had antral biopsies and concomitant CLOtest performed. ISH for H. pylori was done using a 22-base, biotin-labeled oligonucleotide probe complementary to a portion of H. pylori 16s rRNA with the following sequence: 5'-GGACATAGGCTGATCTTAGC-3'. ISH using this probe was specific for H. pylori with no crossreactivity with other bacterial or fungal organisms. Receiver operator characteristic analysis was used to assess the diagnostic performance of ISH and thiazine techniques. ISH and thiazine stains were done on serial sections, reviewed independently, and scored on a graded scale from 1-5 based upon the degree of assurance of H. pylori presence. Diagnostic performance was assessed in "expert" and "nonexpert" pathologist groups with the CLOtest serving as the invariant test for relative test comparison. The ISH test performed slightly better (ROC area 0.9) than the thiazine (ROC area 0.8) in the nonexpert population, but equally well in the "expert" group (ROC area 0.95, 0.95). ISH followed by routine hematoxylin and eosin staining showed detailed mucosal histology with a dramatic visualization of H. pylori along the surface of the foveolar cells with no evidence of lamina propria invasion. In summary, ISH for H. pylori is an excellent test that is specific, easily read, and allows concomitant detailed histologic mucosal examination.

Biopsy↗
PubMed1990

Mediation of 8-hydroxy-guanine formation in DNA by thiazin dyes plus light.

We have discovered that methylene blue plus light mediates the formation of 8-OHdG in DNA. Methylene blue is one of several thiazin dyes and we report here that the other thiazin dyes tested, in combination with white light, are effective in mediating 8-OHdG formation in DNA. The effectiveness of light plus the thiazin dyes in forming 8-OHdG in DNA were as follows: methylene blue greater than azure B greater than azure A greater than toluidine blue greater than thionin. Two other compounds tested; riboflavin and fuschin acid, in combination with light, caused formation of very little, if any, 8-OHdG in DNA. Thiazin dye mediated formation of 8-OHdG in DNA was not inhibited by the spin trap alpha-phenyl-t-butyl nitrone, which supports our previous observations that oxygen free radical scavengers did not inhibit methylene blue plus light mediated 8-OHdG formation in DNA. Ascorbate addition to methylene blue plus DNA, in the absence of light, was ineffective in mediating 8-OHdG formation in DNA.

Animals↗